1. Field of the Invention
The present invention relates to a biosensor for the detection of glucose present in biological fluids such as blood. Particularly, the present invention relates to a biosensor for the amperometric detection of glucose in biological fluids. More particularly, the present invention relates to a biosensor having high accuracy for the amperometric detection of glucose in biological fluids.
2. Description of the Prior Art
It is well known that diabetes is a major health concern. As a general rule, the American Diabetes Association (ADA) recommends that most patients with type I (insulin-dependent) diabetes test glucose three or more times per day. Insulin controls utilization of glucose or sugar in the blood and prevents hyperglycemia which, if left uncorrected, can lead to ketosis. Improper administration of insulin therapy, however, can result in hypoglycemic episodes. Hypoglycemia can cause coma and can be fatal.
Hyperglycemia in diabetics has been correlated with several long-term effects of diabetes such as heart disease, atherosclerosis, blindness, stroke, hypertension and kidney failure. The amount of the insulin injection is related to the blood glucose level. Therefore, the accurate detection of blood glucose is vital for the proper treatment of diabetes. Patients with Type II (non-insulin-dependent) diabetes can also benefit from accurate blood glucose monitoring in the control of their condition by way of diet and exercise.
Since the introduction of the home-use glucose strip and hand-held detection device or meter in the late 1970's, the treatment of diabetes has been greatly improved. However, inaccurate test results inherent in prior glucose measuring systems can lead to the improper treatment of diabetes from time to time. One of the major reasons for inaccurate test results is related to the chemical reagents applied to the glucose strips. Most glucose strips on the market are biosensors based on the use of a mediator and either glucose oxidase (GOD) or pyrroloquinoline quinone dependent glucose dehydrogenase (PQQ-GDH).
The mediator/GOD-based biosensors extend the linear response range for glucose, as compared to the non-mediator based biosensors (hydrogen peroxide measurement is involved). Oxygen-related drawbacks, however, still exist. Mediators are not as efficient at shuttling electrons with the enzyme as is the oxygen molecule. In fact, any oxygen in the sample solution can compete more effectively than the mediators for the enzyme site. The measurements with the mediator/GOD-based biosensors show significantly lower results with increasing oxygen partial pressure (pO2) in the fluid samples. The inaccurate testing results caused by varying oxygen concentration were extensively investigated by several groups (T. Y. Chun, M. Hirose, T. Sawa, M. Harada, T. Hosokawa, Y. Tanaka and M. Miyazaki, Anesth Analg., 75, 993-7, 1994; J. H. Lee, H. Vu, G. J Kost, Clinical Chemistry, 42, S163, 1996; K. Kurahashi, H. Maryta, Y. Usuda and M. Ohtsuka, Crit. Care Med., 25, 231-235, 1997; Z. Tang, R. F. Louie, M. Payes, K. Chang and G. J. Kost, Diabetes Technology & Therapeutics, 2, 349-362, 2000). As warned by Tang et al. (Z. Tang, R. F. Louie, J. H. Lee, D. M. Lee, E. E. Miller, and G. J. Kost, Crit. Care Med., 29, 1062-1070, 2001), special caution should be taken when using the glucose strips for point-of-care glucose testing in critically ill and other patients with unpredictable blood pO2 level.
Additionally, biological specimens contain widely varying oxygen levels. The typical oxygen partial pressure of a venous blood sample is about 32±7 mmHg. In some cases, it can be as low as 20 mmHg. For an arterial sample, one can expect much higher oxygen levels. For the patients who are in o oxygen therapy, the level of arterial pO2 can reach as high as 700 mmHg. Thus, the mediator/GOD-based biosensors could give inaccurate testing results due to the different oxygen concentrations. This becomes more serious when the glucose concentration is at a low level (e.g. glucose concentration less than 70 mg/dL).
To obviate the interference resulting from varying oxygen concentration or so-called “oxygen effect” associated with the use of glucose oxidase, glucose dehydrogenase (GDH) was recently used to replace the oxygen-sensitive glucose oxidase. Glucose dehydrogenase, whose coenzyme is pyrroloquinoline quinone (PQQ), does not interact with oxygen. Therefore, the resultant glucose sensor is unaffected by variable oxygen concentration in the sample. A few products have been developed and marketed using this enzyme such as, for example, Accu-Chek™ Comfort Curve®, Roche Diagnostics, IN, USA, Freestyle®, TheraSense, Alameda, Calif., USA and Ascensia®, Bayer Health Care, Mishawaka, Ind., USA.
The use of glucose dehydrogenase does overcome the problems caused by the oxygen effect. However, glucose dehydrogenase is not as specific as glucose oxidase. It not only reacts with glucose but also reacts with other sugars like galactose and maltose. Both galactose and maltose have a similar structure to glucose. Maltose is composed of two glucose units and galactose differs in structure from glucose only in the position of the hydroxyl group on carbon no. 4. Severe interference can be expected. As a matter of fact, the GDH-based biosensors are more sensitive to maltose and have no discrimination between glucose and galactose (J. D. Newman, C. A. Ramsden, N. D. H. Balazs, Clinical Chemistry, 48, 2071, 2002).
A falsely high glucose reading may be obtained by patients if test strips use a glucose dehydrogenase pyrroloquinoline quinone as the enzyme method. For this reason, the Centers for Medicare & Medicaid Services and ESRD Networks were alerted by the Food and Drug Administration (FDA) on Apr. 18, 2003, to a concern with peritoneal dialysis patients' glucose readings while on Icodextrin Extraneal dialysis solution and the effects of falsely elevated glucose readings because of the interaction of maltose. A false high blood glucose reading could cause a patient to be given more insulin than needed. This, in turn, can lower a patient's blood sugar unnecessarily and can cause a serious reaction including loss of consciousness.
Therefore, what is needed is a glucose measuring system that can provide a more accurate blood glucose reading. What is also needed is a glucose measuring system that can provide a more accurate blood glucose reading by reducing inaccurate test results caused by varying oxygen partial pressure in the fluid sample. What is further needed is a glucose measuring system that can provide a more accurate blood glucose reading by reducing inaccurate test results caused by other sugars in the fluid sample. What is still further needed is a disposable glucose sensor capable of providing more accurate blood glucose readings.